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Felix Stibany, Stine Nørgaard Schmidt, Andreas Schäffer, Philipp Mayer
The aims of the present study were (1) to develop a passive dosing approach for aquatic toxicity testing of liquid substances with very high Kow values and (2) to apply this approach to the model substance dodecylbenzene (DDB, Log Kow = 8.65). The first step was to design a new passive dosing format for testing DDB exactly at its saturation limit. Silicone O-rings were saturated by direct immersion in pure liquid DDB, which resulted in swelling of >14%. These saturated O-rings were used to establish and maintain DDB exposure exactly at the saturation limit throughout 72-h algal growth inhibition tests with green algae Raphidocelis subcapitata...
October 18, 2016: Chemosphere
K Holstein, A Batorova, M Carvalho, K Fijnvandraat, P Holme, K Kavakli, T Lambert, A Rocino, V Jiménez-Yuste, J Astermark
INTRODUCTION: Inhibitor development in people with haemophilia is a serious complication that may require intensive and costly interventions. The goal of inhibitor management should be permanent inhibitor eradication through immune tolerance induction (ITI), but well-designed studies are lacking and the management of patients is therefore defined by the experience and views of the clinician. OBJECTIVES: To explore the current clinical practice and outcome of ITI therapy in Europe and how this may have changed over the last decade, as well as to provide consensus recommendations to guide clinicians in their clinical practice...
October 15, 2016: Thrombosis Research
Fu-Yan Xing, Lin-Lin Guan, Yan-Long Li, Chun-Juan Jia
This work reports a one-step simple synthesis method for functionalized reduced graphene oxide (RGO) nanosheets by a Platanus orientalis leaf extract polyphenol-mediated deoxygenation of graphene oxide (GO). Microscopic and spectroscopic characterization revealed the successful deoxygenation of GO and subsequent stabilization by oxidized polyphenols of plant extract. X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction analyses were used to examine the reduction of GO. Fourier-transform infrared spectroscopy results revealed capping of RGO with oxidized polyphenols of Platanus orientalis extract, which prevented aggregation of graphene sheets...
October 3, 2016: Environmental Toxicology and Pharmacology
Qin Jiang, Xiyue Li, Shanshan Cheng, Yuxiu Gu, Gui Chen, Yuexin Shen, Yixi Xie, Yi Cao
We have recently proposed that the interaction between food components and nanoparticles (NPs) should be considered when evaluating the toxicity of NPs. In the present study, we used THP-1 differentiated macrophages as a model for immune cells and investigated the combined toxicity of low levels of palmitate (PA; 10 or 50μM) and ZnO NPs. The results showed that PA especially at 50μM changed the size, Zeta potential and UV-vis spectra of ZnO NPs, indicating a possible coating effect. Up to 32μg/mL ZnO NPs did not significantly affect mitochondrial activity, intracellular reactive oxygen species (ROS) or release of interleukin 6 (IL-6), but significantly impaired lysosomal function as assessed by neutral red uptake assay and acridine orange staining...
October 18, 2016: Environmental Toxicology and Pharmacology
Eeva Kormi, Johanna Snäll, Anna-Maria Koivusalo, Anna Liisa Suominen, Hanna Thorén, Jyrki Törnwall
PURPOSE: To clarify the effect of systemic dexamethasone (DXM) on pain and postoperative opioid (oxycodone) consumption after blowout fracture surgery. MATERIALS AND METHODS: A prospective randomized observer-blinded trial of 20 patients who had a blowout fracture requiring surgical intervention was conducted. Patients were randomly assigned to receive a total dose of intravenous DXM 30 mg perioperatively or no DXM (controls). Pain was assessed postoperatively using a 10-cm visual analog scale (VAS) each time analgesics (acetaminophen every 6 hours or oxycodone upon request) were administered...
September 26, 2016: Journal of Oral and Maxillofacial Surgery
A Tiwari, H Luo, X Chen, P Singh, I Bhattacharya, P Jasper, J E Tolsma, H M Jones, A Zutshi, A K Abraham
Understanding pharmacological target coverage is fundamental in drug discovery and development as it helps establish a sequence of research activities, from laboratory objectives to clinical doses. To this end, we evaluated the impact of tissue target concentration data on the level of confidence in tissue coverage predictions using a site of action (SoA) model for antibodies. By fitting the model to increasing amounts of synthetic tissue data and comparing the uncertainty in SoA coverage predictions, we confirmed that, in general, uncertainty decreases with longitudinal tissue data...
October 22, 2016: CPT: Pharmacometrics & Systems Pharmacology
L Pelligand, A Soubret, J N King, J Elliott, J P Mochel
The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects...
October 22, 2016: CPT: Pharmacometrics & Systems Pharmacology
I Schütz-Fuhrmann, J Castañeda, Y Reznik, R Aronson, I Conget, S Liabat, S Runzis, S de Portu, O Cohen
The recent OpT2mise randomized trial compared the efficacy of insulin pump therapy and multiple daily injections (MDI) in people with Type 2 diabetes and HbA1c levels that remained ≥64 mmol/mol (8.0%) despite insulin dose optimization [1,2]. During the initial 6-month randomized phase of the study, pump therapy was shown to produce a significant improvement in glycaemic control and a 20% reduction in total daily insulin dose, compared with MDI therapy [1], and these benefits were sustained during the subsequent 6-month extension phase during which all participants received pump therapy [2]...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Daniel L Kenney-Jung, Annamaria Vezzani, Robert J Kahoud, Reghann G LaFrance-Corey, Mai-Lan Ho, Theresa Wampler Muskardin, Elaine C Wirrell, Charles L Howe, Eric T Payne
Febrile infection-related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin-1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super-refractory status epilepticus secondary to FIRES. Anakinra was well-tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES...
October 22, 2016: Annals of Neurology
Qiyue Xia, Hongxia Li, Ying Liu, Kai Xiao
Despite the increasing biomedical applications of gold nanoparticles (AuNPs), their toxicological effects need to be thoroughly understood. In the present study, the genotoxic potential of commercially available AuNPs with varying size (5 nm, 20 nm and 50 nm) were assessed using a battery of in vitro and in vivo genotoxicity assays. In the comet assay, 20 nm and 50 nm AuNPs did not induce obvious DNA damage in HepG2 cells at the tested concentrations, whereas 5 nm NPs induced a dose-dependent increment in DNA damage after 24 h exposure...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Sainath S Kasar, Kiran R Marathe, Amey J Bhide, Abhijeet P Herwade, Ashok P Giri, Vijay L Maheshwari, Pankaj K Pawar
BACKGROUND: Identification and characterization of plant defensive molecules enrich our resources to design crop protection strategies. In particular, plant derived proteinaceous inhibitor(s) of insect digestive enzymes appear to be a safe, sustainable and attractive option. RESULTS: A glycoprotein having non-competitive α-amylase inhibitory activity with molecular weight 8.3 kDa was isolated and purified from seeds of Withania somnifera (WSAI). Its mass spectrometry analysis revealed 59% sequence coverage with Wrightide II type α-AI from Wrightia religiosa...
October 22, 2016: Pest Management Science
Xuehua Piao, Soh Yamazaki, Sachiko Komazawa-Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
: Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar(Hep-low) ) mice. Cellular FLICE-inhibitory protein (cFLIP) expression was downregulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Mathias Kranz, Bernhard Sattler, Solveig Tiepolt, Stephan Wilke, Winnie Deuther-Conrad, Cornelius K Donat, Steffen Fischer, Marianne Patt, Andreas Schildan, Jörg Patt, René Smits, Alexander Hoepping, Jörg Steinbach, Osama Sabri, Peter Brust
BACKGROUND: Both enantiomers of [(18)F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[(18)F]flubatine compared to (-)-[(18)F]flubatine was its higher binding affinity suggesting that (+)-[(18)F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (-)-[(18)F]flubatine in early stages of Alzheimer's disease...
December 2016: EJNMMI Physics
Motahare Soufi, Alireza Kamali-Asl, Parham Geramifar, Arman Rahmim
PURPOSE: Determination of intra-tumor high-uptake area using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging is an important consideration for dose painting in radiation treatment applications. The aim of our study was to develop a framework towards automated segmentation and labeling of homogeneous vs. heterogeneous tumors in clinical lung [(18)F]FDG-PET with the capability of intra-tumor high-uptake region delineation. PROCEDURES: We utilized and extended a fuzzy random walk PET tumor segmentation algorithm to delineate intra-tumor high-uptake areas...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Chi-Liang Cheng, Nai-Jen Liu, Jui-Hsiang Tang, Yen-Lin Kuo, Hsiang-Ling Hung, Yi-Ning Tsui, Bai-Ping Lee, Cheng-Hui Lin
BACKGROUND: A 3-l polyethylene glycol (PEG) solution provided better bowel cleansing quality than a 2-l solution for outpatient colonoscopy. Predictors of suboptimal preparation using a 3-l PEG have not been previously reported. AIMS: To investigate the possible predictors of suboptimal bowel preparation using 3-l of PEG. METHODS: We analyzed a database of 1404 consecutive colonoscopies during a 27-month period at a community hospital. A split-dose PEG regimen was provided for morning colonoscopies, and a same-day PEG regimen was provided for afternoon colonoscopies...
October 21, 2016: Digestive Diseases and Sciences
Eliane Brito Cortez Lima, Caren Nádia Soares de Sousa, Lucas Nascimento Meneses, Yuri Freitas E Silva Pereira, Natália Castelo Branco Matos, Rayanne Brito de Freitas, Nycole Brito Cortez Lima, Manoel Cláudio Azevedo Patrocínio, Luzia Kalyne Almeida Moreira Leal, Glauce Socorro Barros Viana, Silvânia Maria Mendes Vasconcelos
Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments...
October 21, 2016: Journal of Natural Medicines
Alice Indini, Elisabetta Schiavello, Veronica Biassoni, Luca Bergamaschi, Maria Chiara Magni, Nadia Puma, Stefano Chiaravalli, Federica Pallotti, Ettore Seregni, Barbara Diletto, Emilia Pecori, Lorenza Gandola, Geraldina Poggi, Maura Massimino
To assess the long-term safety of administering growth hormone (GH) in patients with GH deficiency due to treatment for childhood medulloblastoma and primitive neuroectodermal tumor (PNET). Data were retrospectively retrieved on children receiving GH supplementation, assessing their disease-free and overall survival outcomes and risk of secondary malignancies using Kaplan-Meier and Cox models. Overall 65 children were consecutively collected from May 1981 to April 2013. All patients had undergone craniospinal irradiation (total dose 18-39 Gy), and subsequently received GH for a median (interquartile range, IQR) of 81 (50...
October 21, 2016: Journal of Neuro-oncology
Mark R Gilbert, Stephanie L Pugh, Ken Aldape, A Gregory Sorensen, Tom Mikkelsen, Marta Penas-Prado, Felix Bokstein, Young Kwok, R Jeffrey Lee, Minesh Mehta
Angiogenesis, a hallmark of glioblastoma, can potentially be targeted by inhibiting the VEGF pathway using bevacizumab, a humanized monoclonal antibody against VEGF-A. This study was designed to determine the efficacy and safety of these regimens in the cooperative group setting. Eligibility included age ≥18, recurrent or progressive GBM after standard chemoradiation. Treatment was intravenous bevacizumab 10 mg/kg and either irinotecan (CPT) 125 mg/m(2) every 2 weeks or temozolomide (TMZ) 75-100 mg/m(2) day 1-21 of 28 day cycle...
October 21, 2016: Journal of Neuro-oncology
Miriam Krischke, Georg Hempel, Swantje Völler, Nicolas André, Maurizio D'Incalci, Gianni Bisogno, Wolfgang Köpcke, Matthias Borowski, Ralf Herold, Alan V Boddy, Joachim Boos
PURPOSE: Doxorubicin is a key component in many pediatric oncology treatment regimens; still pharmacology data on which current dosing regimens are based are very limited. METHODS: We conducted a multinational pharmacokinetic study investigating age dependency of doxorubicin metabolism and elimination in children with cancer. One hundred and one patients treated with doxorubicin according to a cancer-specific national or European therapeutic trial were recruited...
October 21, 2016: Cancer Chemotherapy and Pharmacology
Andrew Jeyaruban, Muriel Soden, Sarah Larkins
To examine the management of gout in general practice in Townsville, Australia, and to explore comorbid conditions in patients with gout. Study will also explore how closely guidelines are being followed in managing gout. Retrospective chart review was conducted from May to November 2014 in three general practices in Townsville. Registers for patients were established by searching "gout" and "gouty arthritis". Three hundred and twenty-one patients were included in the study after excluding inactive patients, patients below age of 18 and patients with cancer...
October 21, 2016: Rheumatology International
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